Fetal Genome Profiling Via Trophoblast Cells

Fetal Genome Profiling After Non-Invasive Isolation of Trophoblast Cells

The objective of this study is to utilize trophoblast cells accumulating in the endocervical canal at the beginning of pregnancy for non-invasive prenatal testing. If we are able to validate that trophoblast cells obtained at an early gestational age can be reliably used for prenatal testing, there is great potential to improve early pregnancy management and counseling options for potential parents. The target population will be all women between the age of 18-45 undergoing care at the Center for Reproductive Medicine (CRM) in order to achieve a pregnancy.

Study Overview

• Status: Terminated
• Conditions: Fetal Growth Retardation
• Intervention / Treatment: Diagnostic test: Fetal Genome Profiling.

Detailed Description

The primary purpose of the study is to validate trophoblast retrieval and isolation from the cervix (TRIC) as a means of reliable non invasive prenatal genetic diagnosis (for both chromosomal abnormalities, as well as single gene defects).

The study population will be recruited from women, age 18 to 45, presenting to the Center for Reproductive Medicine (CRM) for medical care with the desire to become pregnant. Patients that achieve pregnancy will be invited by a physician to participate in the study. If prospective subjects agree to participate, they will meet with a co-investigator to go through the informed consent process.

Subjects will undergo a one-time non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at approximately 5-6 weeks of pregnancy as the experimental procedure for the study. TRIC is performed with ThinPrep kits using a cytobrush, the same method of Pap smear collection which is a routine part of prenatal care. The fetal trophoblast cells will then be isolated using immunomagnetic isolation. Once isolated, DNA fragmentation, fluorescent in situ hybridization (FISH), and single-cell PCR methods will be utilized to analyze the fetal genome at single nucleotide resolution. Any abnormal results identified by TRIC will be communicated to the subjects' by their physician in the office who will counsel them on the potential meaning of the results and recommend follow up testing to be ordered by their obstetrician to confirm results.

The cellular analysis from TRIC will then be compared to results obtained from CVS, amniocentesis, preimplantation genetic screening (PGS) and/or preimplantation genetic diagnosis (PGD) of the transferred embryo(s), or cytogenetic testing of fetal tissue in the event of miscarriage or pregnancy termination for validation. In the event that a patient does not undergo any of the aforementioned testing, TRIC results will be compared to birth outcomes.

Subjects will be followed via medical records through the final outcome of the pregnancy, whether termination of pregnancy, miscarriage, or live birth. If the pregnancy results in termination of pregnancy or miscarriage, cytogenetic testing of the fetus will be completed as standard care with the results compared to those obtained through TRIC testing. If the pregnancy results in live birth, basic neonatal information will be obtained via medical records, specifically whether the neonate is diagnosed with a disorder that can be identified through single gene testing (see attached table).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mitasha Joseph-Sohan, RN, MPA; Phone Number: 646-962-3382; Email: mij2008@med.cornell.edu
• Study Contact Backup: Name: Rodriq Stubbs, MS. NP; Phone Number: 646-962-3276; Email: res2011@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women 18 to 45 who achieve a pregnancy during study time period.
• If pregnancy result in miscarriage, cytogenetic testing must be completed on the product of conception.

Exclusion Criteria:

• Women whose cervical sample collection containing inadequate number of trophoblast cells for analysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fetal Genome Profiling; Trophoblast cells will be collected from the cervix approximately 5-6 weeks once pregnancy is achieved.	Diagnostic test: Fetal Genome Profiling.; Once pregnancy is achieved, patients will undergo non-invasive collection of trophoblast cells (trophoblast retrieval and isolation from the cervix, TRIC) at an early gestational age, approximately 5-6 weeks. The patient will also be screened with blood work for carrier status for genetic conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of chromosomal anomalies as detected via fetal genome analysis of trophoblast cells	Trophoblast cells isolated from the cervix will be used to detect chromosomal anomalies occurrences as a means of non-invasive prenatal screening.	6 weeks post pregnancy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of chromosomal anomalies detected via trophoblast cell analysis as compared to occurrence of chromosomal anomalies detected via preimplantation genetic testing (PGT), chorionic villi sampling (CVS), amniocentesis, or cytogenetic results.	Occurrence of chromosomal anomalies detected via trophoblast cells analysis will be compared to the occurrence of chromosomal anomalies detected via either PGT, CVS, amniocentesis, or cytogenetic which ever is available for validation.	16 weeks post pregnancy

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Kangpu Xu, PhD, DVM, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): February 14, 2021
• Study Completion (Actual): February 2, 2023

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: February 5, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Growth Retardation
• Other Study ID Numbers: 1703018076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No